NeuroMolecular Medicine

, Volume 15, Issue 3, pp 549–569 | Cite as

Nicotine Prevents Synaptic Impairment Induced by Amyloid-β Oligomers Through α7-Nicotinic Acetylcholine Receptor Activation

  • Nibaldo C. Inestrosa
  • Juan A. Godoy
  • Jessica Y. Vargas
  • Macarena S. Arrazola
  • Juvenal A. Rios
  • Francisco J. Carvajal
  • Felipe G. Serrano
  • Ginny G. Farias
Original Paper


An emerging view on Alzheimer disease’s (AD) pathogenesis considers amyloid-β (Aβ) oligomers as a key factor in synaptic impairment and rodent spatial memory decline. Alterations in the α7-nicotinic acetylcholine receptor (α7-nAChR) have been implicated in AD pathology. Herein, we report that nicotine, an unselective α7-nAChR agonist, protects from morphological and synaptic impairments induced by Aβ oligomers. Interestingly, nicotine prevents both early postsynaptic impairment and late presynaptic damage induced by Aβ oligomers through the α7-nAChR/phosphatidylinositol-3-kinase (PI3K) signaling pathway. On the other hand, a cross-talk between α7-nAChR and the Wnt/β-catenin signaling pathway was revealed by the following facts: (1) nicotine stabilizes β-catenin, in a concentration-dependent manner; (2) nicotine prevents Aβ-induced loss of β-catenin through the α7-nAChR; and (3) activation of canonical Wnt/β-catenin signaling induces α7-nAChR expression. Analysis of the α7-nAChR promoter indicates that this receptor is a new Wnt target gene. Taken together, these results demonstrate that nicotine prevents memory deficits and synaptic impairment induced by Aβ oligomers. In addition, nicotine improves memory in young APP/PS1 transgenic mice before extensive amyloid deposition and senile plaque development, and also in old mice where senile plaques have already formed. Activation of the α7-nAChR/PI3K signaling pathway and its cross-talk with the Wnt signaling pathway might well be therapeutic targets for potential AD treatments.


α7-nAChR Aβ oligomers Wnt signaling pathway 



We thank Dr. Rodrigo Varas for his help with the electrophysiological studies of the α7-nAChR. This work was supported by a grant from FONDECYT No 120156 to N.C.I; predoctoral fellowships from CONICYT to G.G.F., M.S.A. F.G.S., J.A.R. and from Fundación Gran Mariscal de Ayacucho to J.Y.V. The Basal Center of Excellence in Science and Technology CARE was funded by CONICYT/PFB 12/2007.

Supplementary material

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Supplementary material 1 (DOC 46 kb)
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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Nibaldo C. Inestrosa
    • 1
    • 2
  • Juan A. Godoy
    • 1
    • 2
  • Jessica Y. Vargas
    • 2
  • Macarena S. Arrazola
    • 2
  • Juvenal A. Rios
    • 2
  • Francisco J. Carvajal
    • 1
  • Felipe G. Serrano
    • 2
  • Ginny G. Farias
    • 3
  1. 1.Centro de Envejecimiento y Regeneración (CARE)Pontificia Universidad Católica de ChileSantiagoChile
  2. 2.Departamento de Biología Celular y Molecular, Facultad de Ciencias BiológicasPontificia Universidad Católica de ChileSantiagoChile
  3. 3.Cell Biology and Metabolism Program, Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institutes of HealthBethesdaUSA

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